The Impact of SGLT2 Inhibitors and GLP-1 Receptor Agonists on 24-hour Urine Parameters

Background: Emerging data suggest sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) may lower stone risk. Methods: We characterized 24-hour urine parameters among individuals with kidney stone disease receiving these agents using Medicare claims from beneficiaries with urine collections processed by a central laboratory between January 2010 and December 2019. We identified a cross-sectional cohort with diabetes and a prescription fill for SGLT2i or GLP-1RA within the six months preceding their urine collection and matched controls. We additionally identified a subset of patients who performed two collections and had a prescription fill for SGLT2i or GLP-1RA before the second collection, but not the first. We compared across 24-hour urinary parameters in both cohorts and adjusted for multiple comparisons. Results: The cross-sectional cohort included 124 patients with a prescription fill for SGLT2i (and 620 matched controls), and 349 patients with a prescription fill for GLP-1RA (and 349 matched controls). Compared to controls, patients on SGLT2i had a higher mean urine citrate (838 mg vs. 636 mg; p<0.01) and volume (2.4L vs. 2.0 L; p<0.01) with improved calcium phosphate supersaturation (p<0.01). Lower urine pH and higher sulfate, and uric acid were observed in the SGLT2i group (p<0.01 for each). There were no significant differences in urine parameters with GLP-1RA. In the longitudinal analyses of SGLT2is (59 patients) and GLP-1RAs (154 patients), there were no significant differences in urinary parameters. Conclusions: SGLT2is were associated with higher urine volume and citrate in a cross-sectional cohort. GLP-1RA were not associated with changes that would reduce stone risk.